Miller Fisher syndrome: axonal, demyelinating or both?

Controversy exists concerning whether Miller Fisher syndrome (MFS) is the result of a predominantly axonal or demyelinating polyneuropathy and whether the Guillain-Barré syndrome variant of acute ataxia and areflexia without ophthalmoplegia, ataxic Guillain-Barré syndrome (atxGBS), has a distinct pathophysiology. We explored these issues by reviewing the electrophysiologic features of 6 patients with MFS and 2 patients with atxGBS. EMG laboratory records were reviewed and electrophysiologic findings were categorized as axonal or demyelinating neuropathy using previously defined criteria. Of the 6 patients with MFS, 5 had electrophysiologic evidence suggestive of an axonal, predominantly sensory polyneuropathy; only 1 patient met criteria for demyelinating polyneuropathy. Both patients with atxGBS had demyelinating sensorimotor polyneuropathy. Electrophysiologic abnormalities in MFS typically suggest a predominantly axonal, sensory polyneuropathy, though demyelinating forms occur and may be under-diagnosed using current criteria. AtxGBS, in our experience, is a predominantly demyelinating polyneuropathy.     

Comorbidity of bipolar and eating disorders: distinct or related disorders with shared dysregulations?

BACKGROUND: The co-occurrence of bipolar and eating disorders, though of major clinical and public health importance, remains relatively unexamined. METHODS: In reviewing the literature on this comorbidity, we compared bulimia, anorexia nervosa, bulimia nervosa, binge eating disorders and bipolar disorders on phenomenology, course, family history, biology, and treatment response. RESULTS: Epidemiological studies show an association between subthreshold bipolar disorder and eating disorders in adolescents, and between hypomania and eating disorders, especially binge eating behavior, in adults. Of the clinical studies, most show that patients with bipolar disorder have elevated rates of eating disorders, and vice versa. Finally, the phenomenology, course, comorbidity, family history, and pharmacologic treatment response of these disorders show considerable overlap on all of these parameters. In particular, on phenomenologic grounds--eating dysregulation, mood dysregulation, impulsivity and compulsivity, craving for activity and/or exercise--we find many parallels between bipolar and eating disorders. Overall, the similarities between these disorders were more apparent when examined in their spectrum rather than full-blown expressions. LIMITATIONS: Despite an extensive literature on each of these disorders, studies examining their overlap across all these parameters are relatively sparse and insufficiently systematic. CONCLUSIONS: Nonetheless, the reviewed literature leaves little doubt that bipolar and eating disorders--particularly bulimia nervosa and bipolar II disorder--are related. Although several antidepressants and mood stabilizers have shown promise for eating disorders, their clinical use when these disorders co-exist with bipolarity is still very much of an art. We trust that this review will stimulate more rigorous research in their shared putative underlying psychobiologic mechanisms which, in turn, could lead to more rational targeted treatments.     

Eating disorders in midlife women: A perimenopausal eating disorder?

Eating disorders afflict women across the lifespan with peak onset during critical or sensitive developmental periods of reproductive hormone change, such as puberty. A growing body of research supports the role of reproductive hormones, specifically estrogen, in the risk for eating disorders and related symptomatology in adolescence and young adulthood. Like puberty, perimenopause is characterized by estrogen change and may also present a window of vulnerability to eating disorder development. Here, we discuss the evidence that suggests perimenopause indeed may be a vulnerable period for the development or redevelopment of an eating disorder for midlife women. Drawing from what is known about the influence of estrogen on eating disorders at younger ages and from other psychiatric disorders with similar risk trajectories (i.e., perimenopausal depression), we describe a potential mechanism of risk for a perimenopausal eating disorder and how this can be explored in future research. Investigating vulnerability to perimenopausal eating disorders will clarify eating disorder etiology, identify reproductive stage-specific risk profiles, and guide future treatment directions.     

Polycystic ovaries and eating disorders: Are they related?

A cross-sectional observational study was used to investigate the reported association between polycystic ovarian syndrome and bulimia nervosa in a group of young, post-menarcheal women in the normal population. Volunteers aged 18-25 years were recruited from two universities and two general practice surgeries in Oxford. A total of 230 women completed an interviewer-based eating disorder examination, which was used to diagnose bulimia nervosa and its variants, and to assess eating behaviour. Transabdominal ultrasound was used to diagnose the presence or absence of polycystic ovaries. Symptoms of polycystic ovarian syndrome were assessed using menstrual history, anthropometric measurements, clinical observation of acne and hirsutism, and biochemical analysis of a fasting blood sample. A total of 30% of all participants described episodes of overeating and 4% had used extreme methods of weight control. Two women were diagnosed with bulimia nervosa, and five women with binge-eating disorder; however, these diagnoses were not associated with polycystic ovaries. Scores for dieting and overall eating disorder symptoms in the polycystic ovary groups were not significantly higher than those for women with normal ovaries, and therefore the suggestion that polycystic ovaries predispose towards the development of eating disorders is not supported by this study.     

Say-Barber-Biesecker-Young-Simpson syndrome and Genitopatellar syndrome: Lumping or splitting?

The Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) and Genitopatellar syndrome (GTPTS) are 2 rare but clinically well-described diseases caused by de novo heterozygous sequence variants in the KAT6B gene. Both phenotypes are characterized by significant global developmental delay/intellectual disability, hypotonia, genital abnormalities, and patellar hypoplasia/agenesis. In addition, congenital heart defects, dental abnormalities, hearing loss, and thyroid anomalies are common to both phenotypes. This broad clinical overlap led some authors to propose the concept of KAT6B spectrum disorders. On the other hand, some clinical features could help to differentiate the 2 disorders. Furthermore, it is possible to establish a genotype-phenotype correlation when considering the position of the sequence variant along the gene, supporting the notion of the 2 disorders as really distinct entities.     

Digital anomalies,microcephaly, and normal intelligence: New syndrome or Feingold syndrome?

We present four patients—two boys and their mother and an unrelated girl—with microcephaly, normal intelligence, and digital abnormalities. The hand abnormalities are characterized by brachydactyly with radial clinodactyly of the fourth and fifth fingers, ulnar clinodactyly of the second fingers, and an increased space between the second and third fingers associated with an abnormal palmar crease that extends to the ulnar border. The foot abnormalities include short toes with syndactyly of the fourth and fifth toes. The mother has normal intelligence, and her sons and the unrelated girl have normal development. Although similar digital abnormalities, microcephaly, and normal intelligence were described by Feingold in patients with gastrointestinal atresia, we think that our patients' findings represent a different condition. The most likely mode of inheritance is autosomal dominant. The clinical recognition of this syndrome will allow for appropriate genetic counseling as well as provision of information on natural history, i.e., normal intelligence. Am. J. Med. Genet. 69:240–244, 1997. © 1997 Wiley-Liss, Inc.     

Anorexia nervosa: obsessive-compulsive disorder,obsessive-compulsive personality disorder,or neither?

Anorexia nervosa (AN) is a severe and often chronic disorder with uncertain aetiology and poor prognosis. New approaches to the understanding of the disorder are needed in order to aid the development of more effective treatments. Several authors have suggested that AN has a considerable overlap with obsessive-compulsive disorder (OCD) and that this may reflect common neurobiological, genetic, or psychological elements. However, more recent studies have suggested that AN may have a closer relationship with obsessive-compulsive personality traits such as those found in obsessive-compulsive personality disorder (OCPD). In this paper, evidence for links between the three conditions is reviewed, suggestions for further research are outlined and possible implications for the treatment of AN are presented.     

γδ T cells and multiple sclerosis: Friends, foes, or both?

Multiple sclerosis (MS) is a debilitating CNS disease characterized by demyelination and neuro-axonal loss. Though the exact etiology is still unknown, accumulated evidence points to the immune system being involved in the MS disease-process. Both ill-fated adaptive and innate immune responses can potentially contribute to the etiopathogenesis. We have been interested in deciphering how innate immunity might be involved; in particular, the role of γδ T cells. In this review, we discuss the current understanding about γδ T cells and describe the evidence implicating them in myelin injury, neurotoxicity, and immunoregulation in the development of MS.     

A review of cognitive neuropsychiatry in the taxonomy of eating disorders: State,trait, or genetic?

A greater understanding of neuropsychological traits in eating disorders may help to construct a more biologically based taxonomy. The aim of this paper is to review the current evidence base of neuropsychological traits in people with eating disorders. Evidence of difficulties in set shifting, weak central coherence, emotional processing difficulties, and altered reward sensitivity is presented for people both in the acute and recovered phase of the illness. These traits are also seen in first degree relatives. At present there is limited research linking these neuropsychological traits with genetic and neuroanatomical measures. In addition to improving the taxonomy of eating disorders, neuropsychological traits may be of value in producing targeted treatments.     

Child with overgrowth,pigmentary streaks,polydactyly, and intestinal lymphangiectasia: macrocephaly-cutis marmorata telangiectatica congenita syndrome or new disorder?

Since 1988, when Rogers first described a boy with anophthalmia associated with esophageal atresia, eight similar cases have been reported. These patients lend support to the hypothesis that this association of congenital anomalies constitutes a discrete entity, although the etiology is still unknown. We report a patient with this combination of malformations as well as a marked hypoplasia of the entire left half of the body.     

Color sensitivity and mood disorders: biology or metaphor?

BACKGROUND: A familiar but overlooked symptom in affective disorders is patient self-report of alterations in color sensitivity. Anecdotal and empirical evidence have suggested an association between mood and color sensitivity. The purpose of this pilot study was to test three hypotheses concerning the relationship between mood disorders and color sensitivity. METHODS: Using a cross-sectional survey design consisting of a sample of 120 inpatients and outpatients, color sensitivity was assessed by the patient's response to a self-report depression scale item, "I notice that everything seems gray/cloudy/drab/lacking color". RESULTS: Color sensitivity significantly correlated with depression in the total sample (P=0.001).The other two hypotheses approached significance but were not supported. DISCUSSION: These findings suggest there is evidence that color sensitivity is impaired during depression. Further research using a larger, more homogeneous sample and longitudinal design whereby measures of mood and color sensitivity are correlated before, during, and after treatment in depressed and manic patients would be justified. A study using ophthalmological instrumentation to measure color sensitivity would provide objective, 'hard' evidence of the association between color sensitivity and depression. CONCLUSIONS: Whether color perception is metaphorically reported by patients to describe their mood or a biological phenomenon remains to be validated. Findings seem to lend support to the conclusion that abnormalities in brain function alter retinal function.     

Cryptophthalmos,dental and oral abnormalities,and brachymesophalangy of second toes: New syndrome or Fraser syndrome?

We report on an 8‐year‐old Thai girl with bilateral complete cryptophthalmos, facial asymmetry, delayed bone age, brachymesophalangy and medial deviation of the second toes, and dental anomalies. The dental anomalies consist of delayed dental development, congenital absence of the second premolars, microdontia of the deciduous molars. A fibrous band of the buccal mucosa was found. Dental anomalies are rare among patients with Fraser syndrome. They have not been reported in either isolated or other syndromic cryptophthalmos. The oral manifestations and brachymesophalangy of the second toes found in our patient may represent newly recognized findings associated with cryptophthalmos or they may represent a newly recognized syndrome. © 2001 Wiley‐Liss, Inc.     

Cryptophthalmos, dental and oral abnormalities, and brachymesophalangy of second toes: new syndrome or Fraser syndrome?

We report on an 8-year-old Thai girl with bilateral complete cryptophthalmos, facial asymmetry, delayed bone age, brachymesophalangy and medial deviation of the second toes, and dental anomalies. The dental anomalies consist of delayed dental development, congenital absence of the second premolars, microdontia of the deciduous molars. A fibrous band of the buccal mucosa was found. Dental anomalies are rare among patients with Fraser syndrome. They have not been reported in either isolated or other syndromic cryptophthalmos. The oral manifestations and brachymesophalangy of the second toes found in our patient may represent newly recognized findings associated with cryptophthalmos or they may represent a newly recognized syndrome.     

β-cell regeneration: Neogenesis,replication or both?

Both type I and type II diabetes are characterized by beta-cell loss and dysfunction. Therefore, a major goal of diabetes therapy is to promote the formation of new beta-cells, either in vitro for transplantation or in vivo, i.e., beta-cell regeneration. The question of whether beta-cell regeneration occurs by replication of preexisting beta-cells or by neogenesis from a precursor within the pancreas is a major focus of interest. Lineage-tracing studies have found evidence only for beta-cell replication, while earlier studies based upon the appearance of insulin-positive cells in areas outside of islets formed the basis for the belief that neogenesis from precursors can occur in adult animals. Recently, we found that nonendocrine pancreatic epithelial cells could be induced to undergo endocrine differentiation under the influence of inductive factors from the human fetal pancreas. One possibility is that, similar to models of hepatocyte regeneration, beta-cells can arise either by neogenesis or replication, depending on the particular stimulus. Clearly, understanding the nature and control of beta-cell regeneration is critical for success in efforts to treat diabetes by beta-cell replacement.     

Subjective fatigue and subjective sleepiness: two independent consequences of sleep disorders?

The objective of this investigation was to evaluate subjective fatigue versus subjective sleepiness as independent consequences of sleep disorders. Furthermore, we tried to explore how these symptoms relate to alertness, depressive symptoms and illness intrusiveness. In a prospective observational study, 283 sleep-disordered patients referred to a hospital-based sleep laboratory for various indications over a 1-year period were evaluated vis-à-vis fatigue and sleepiness. All patients completed five subjective questionnaires, underwent objective sleep recording and attended a clinical interview with a sleep specialist. The subjective questionnaires included the Epworth Sleepiness Scale, the Fatigue Severity Scale, the Toronto Hospital Alertness Test, the Illness Intrusiveness Rating Scale and the Center for Epidemiologic Studies-Depression Scale. Only 4% of the total sample was referred to the sleep clinic due to a complaint of excessive fatigue compared with 17% for excessive daytime sleepiness. However, during the assessment, 64% of referred patients reported pathological fatigue without overlap of sleepiness and only 4% reported pathological sleepiness without overlap of fatigue. Pearson's correlation analysis indicated a weak association (r=0.18) between subjective fatigue and sleepiness in the total sample. Analysis of variance testing showed strong association between those patients with prominent fatigue and depressive symptoms (P<0.01) and illness intrusiveness (P<0.001). The findings support the notion that subjective fatigue and sleepiness can be independent manifestations of sleep disorders. Furthermore, predominantly fatigued individuals with sleep disorders seem vulnerable to additional negative consequences due to possible interplay between amplified fatigue and psychological distress.